Device and method for the administration of a substance

ABSTRACT

The present invention relates to an aerosol spray device ( 10, 20, 30, 40 ) for administration of a substance, specifically a substance having a disagreeable taste, such as nicotine, to the oral cavity of a subject; to an actuator ( 16, 26, 36, 46 ) included in said spray device and to methods for delivering the substance.

TECHNICAL FIELD

[0001] The present invention relates to an aerosol spray device foradministration of a substance, specifically a substance having adisagreeable taste, such as nicotine, to the oral cavity of a subject;to an actuator included in said spray device and to methods fordelivering the substance.

BACKGROUND OF THE INVENTION

[0002] Oral administration of a substance, such as a drug or medicament,is frequently used, such as in the form of aerosol sprays for inhalationfor the treatment of asthma. Another area of oral administration of asubstance, such as a drug or medicament, is the area ofnicotine-replacement therapy to give up smoking. Several apparatuses forthe administration of nicotine containing aerosols have been described,such as in U.S. Pat. No. 5,810,018, U.S. Pat. No. 4,593,572 and U.S.Pat. No. 4,945,929.

[0003] One problem experienced with such medicaments being inhaled oradministered locally in the oral cavity is the effects of substanceshaving a disagreeable taste being distributed to the oral cavity of anindividual. This is a problem in general with irritating and bad tastingdrug substances and specifically a problem with nicotine. Suchsubstances are influencing the taste and irritation sensory sites in themouth and can cause problems when administered locally in the oralcavity to be absorbed through the oral mucosa. This is a particularproblem when the drug is deposited on the back of the tongue where thereis a high density of taste buds and in the upper throat where reflexesfor nausea can be triggered.

[0004] When using traditional equipment for oral administration of anaerosol spray, a large part of the administered dose will end up in thewhole oral cavity, the pharynx and/or the bronchial tree of therespiratory tract depending on the droplet size. Medicaments associatedwith inhalation, such as asthma drugs, are preferentially appliedlocally in the respiratory tract and lungs for a rapid and efficienteffect. Still, not all orally sprayed medicaments are to be delivered tothe respiratory tract and lungs, but are given locally in the oralcavity for uptake through the oral mucous membrane.

[0005] One such medicament is nicotine. Nicotine is an organic compoundthat is the principal alkaloid of tobacco. Nicotine is the chiefaddictive ingredient in the tobacco used in cigarettes, cigars, snuffand the like. Nicotine is also an addictive drug, though, and smokerscharacteristically display a strong tendency to relapse after havingsuccessfully stopped smoking for a time. Nicotine is the worlds secondmost used drug, after caffeine from coffee and tea.

[0006] The main problem with tobacco smoking is its enormousimplications on health. Today it is estimated that smoking relateddiseases cause some 3-4 million deaths per year. This grim consequenceof tobacco smoking has urged many medical associations and healthauthorities to take very strong actions against the use of tobacco.

[0007] Tobacco smoking can result in a dependence disorder. The WHO hasin its International Classification of Disorders a diagnosis calledTobacco Dependence. Others like the American Psychiatric Associationcall the addiction Nicotine Dependence. Even though tobacco smoking isdecreasing in many developed countries today it is hard to see how thesocieties could get rid of the worlds second most used drug.

[0008] Nicotine containing medications are currently the dominatingtreatments for tobacco dependence. There is also evidence of broader useof these medications like for smoking reduction and long termmaintenance/substitution.

[0009] When smoking a cigarette, nicotine is quickly absorbed into thesmoker's blood and reaches the brain within eight seconds afterinhalation. The poisonous, toxic, carcinogenic, and addictive nature ofsmoking has provided efforts for methods, compositions and devices,which help in breaking the habit of smoking cigarettes.

[0010] For those who are unable to give up smoking there are severalways and forms of nicotine replacement products available on the market;such as nicotine gum. Several methods and means have been described fordiminishing the desire of a subject to use tobacco, which comprises thestep of administering to the subject nicotine or a derivative thereof asdescribed in e.g. U.S. Pat. No. 5,939,100, U.S. Pat. No. 4,967,773, U.S.Pat. No. 865,026, U.S. Pat. No. 940,521. Aerosol compositions aredescribed in GB 1 528 391, GB 2 030 862, U.S. Pat. No. 5,810,018, EP 0557 129 and U.S. Pat. No. 4,593,572 and are adapted to be sprayed intothe mouth of the user. Also, inhaling devices resembling a cigarette areknown for ingestion of nicotine vapours orally as suggested in U.S. Pat.No. 5,167,242. Finally, ways of administrating nicotine is by way ofdelivering directly into the nasal cavity is known from U.S. Pat. No.4,579,858, DE 32 41 437 and WO/93 127 64. Said means and methods addressthe problems associated with addiction to nicotine.

[0011] However, as stated above, a major drawback with the presentlyavailable nicotine containing aerosol spray devices is the fact thatthey deliver a large part of the dose in the back of the mouth cavity.This generally results in an experience of a bad and disagreeable taste,nausea and other irritations.

[0012] Several proposals have been provided for solving said problem ofbad and disagreeable taste. Flavourants, such as tobacco flavouring,menthol or methyl salicylate, for example, may be added to impregnatesuch nicotine taste to produce an oral nicotine spray with apharmacologically acceptable flavour. U.S. Pat. No. 4,967,773 describesthe addition of liquorice, cocoa, aniseed and peppermint to a nicotinelozenge to avoid the bad taste of nicotine.

[0013] Still, none of the above mentioned means and methods addressesthe problems associated with the bad taste of nicotine in any other waybut addition of different flavouring agents.

[0014] Even though flavouring to conceal the bad taste of a medicamentmay partly circumvent the problem of bad tasting drugs it includes thefurther step in the production of the medicament of adding the desiredflavouring agent. Moreover, addition of a flavourant may not conceal thetaste or the irritating effect very well or long enough.

[0015] WO 95/20 411 describes a method of converting a medicament to aform usable for administration of the medicament to the airways orrespiratory tracts of mammals. This is to bring the medicament to thelocation where it will do most good on people suffering from respiratoryproblems, such as asthma.

[0016] WO 99/6550 describes an inhalation device for providing pulmonarymedicament for inhalation where the inhalation device includes a vortexgenerator. The vortex created through this vortex generator gives thesmoker a feeling of “mouthfulness” close to what is experienced whensmoking a cigarette.

[0017] GB 2 308 992 A describes a nebulizer for administering an aerosolto the lungs of patients requiring respiratory therapy, by producing alarge number of small droplets and fewer large droplets in the aerosolproduced by the nebulizer.

[0018] All said devices for oral administration describe means andmethods for specific local delivery into the respiratory tracts, wherethe aim is to avoid as much as possible of the aerosol to deposit in theoral cavity.

[0019] Thus, there is a need for a delivery system, which solves theabove mentioned problems associated with oral administration ofsubstances, such as drugs and medicaments, having a bad, irritating orotherwise disagreeable taste and at the same time achieve an efficientmedication, i.e. an efficient blood concentration of the substance.

SUMMARY OF THE INVENTION

[0020] The main object of the present invention is to provide means andmethods for overcoming the disadvantages and solving the problemsassociated with the foregoing known devices for oral delivery of asubstance having a bad or disagreeable taste and/or being a source ofirritation.

[0021] A further object of the present invention is to provide means andmethods for overcoming the above disadvantages and solving the aboveproblems while at the same time achieving an efficient absorption of thesubstance.

[0022] Further objects of the invention will appear from the followingdescription and the appending claims.

[0023] To fulfil these objects the present invention relates to anaerosol spray device for administering a substance to the oral cavity ofa subject, said aerosol spray device comprising an actuator having anactuator head with a defined axis and at least one orifice the actuatorhead being constructed to dispense the aerosol spray containing thesubstance in the front of the oral cavity of the subject.

[0024] The invention also relates to an actuator being adapted to beused in such an aerosol spray device.

[0025] Furthermore, the invention refers to a method for oraladministration of a substance to a subject, comprising delivering anaerosol spray containing the substance to the front of the oral cavityof the subject.

[0026] In one embodiment the invention refers to a method of assistingin the reduction of the desire of a subject to use nicotine or nicotinecontaining compositions, comprising delivering a nicotine containingaerosol spray to the front of the oral cavity of the subject.

[0027] By means of the means and methods provided by the presentinvention a bad and disagreeable taste of a drug may be reduced orsubstantially avoided resulting in better compliance, less irritationand other untoward effects, which in turn means more efficient therapy.

[0028] We have surprisingly found that by administering the above typeof substance in the front of the oral cavity, such as below the tongueor between the lips and the teeth the experience of bad and disagreeabletaste and irritation may be largely reduced or substantially eliminatedat the same time as the effect of the substance is substantiallymaintained.

SHORT DESCRIPTION OF DRAWINGS

[0029]FIG. 1A shows a side elevation view of a first embodiment of anaerosol spray device according to the invention,

[0030]FIG. 1B shows a front view of the top portion of FIG. 1A,

[0031]FIG. 2A shows a side elevation view of a second embodiment of anaerosol spray device according to the invention,

[0032]FIG. 2B shows a front view of the top portion of FIG. 2A,

[0033]FIG. 3A shows a side view of a third embodiment of a top portionfor use with an aerosol spray device according to the invention,

[0034]FIG. 3B shows a front view of the top portion of FIG. 3A,

[0035]FIG. 4A shows a side view of a fourth embodiment of a top portionto be used with an aerosol spray device according to the invention, and

[0036]FIG. 4B shows a front view of the top portion of FIG. 4A.

DETAILED DESCRIPTION OF THE INVENTION

[0037] Definitions

[0038] The term “aerosol spray device” is intended to mean a device foratomisation, dispersion and mixing of a fluid or powdery substance forthe production of an aerosol.

[0039] The term “actuator” is intended to mean a means for deliveringand controlling a spray or fine mist. The actuator comprises, for thispurpose, an actuator head having an orifice for generation of a desiredspray or spray pattern.

[0040] The term “administration to the oral cavity” is intended to meandelivering to and absorption in the oral cavity of a subject.

[0041] The term “disagreeable taste” is intended to mean any taste,which in general is regarded as bad, nasty, or gives negativeassociations, such as nausea and indigestion, or is a source ofirritation to the recipient.

[0042] The term “irritation ”is intended to mean irritating effects suchas burning, acrid or stinging effects or the like.

[0043] The Aerosol Spray Device

[0044] In order to avoid a bad or disagreeable taste and irritation froma medicine substance, such as nicotine, we have found that the sprayfrom a spray actuator has to be delivered to the front of the oralcavity of the subject receiving the substance. This is accomplished bymeans of a spray device according to the invention as described below inconjunction with the drawings. The spray or spray pattern delivereddeposits the sprayed liquid in the front of the oral cavity either infront of the mandibular front teeth between the lips and the teeth, justbehind the teeth or under the tongue, which thereby minimises bad tasteand irritation. The actuator could be constructed according to, but notlimited to the appended drawings.

[0045] With reference to FIG. 1A there is shown an aerosol spray device10. Said spray device includes a spray bottle 11 adapted to include afluid and a top portion 17. The top portion 17 includes a cap portion 12and an actuator 16 according to the invention. The actuator 16, having adefined axis a-a, includes a tube portion 13 and an actuator head 14being provided with two orifices 15. A front view of the top portion 17of said aerosol spray device 10 is shown in FIG. 1B. The actuator head14 has the form of a plate and the two orifices 15 are placed one oneach side of the actuator head 14 along the actuator head axis a-a. Thefluid included in the spray bottle 11 is in this embodiment dispersedsubstantially perpendicular to the axis a-a of the actuator head 14, asshown in FIG. 1B.

[0046] In FIG. 2A there is shown a second embodiment of an aerosol spraydevice 20. In analogy with the embodiment of FIGS. 1A and B said spraydevice includes a spray bottle 21 and a top portion 27. The top portion27 includes a cap portion 22 and an actuator 26 according to theinvention. The actuator 26 includes a tube portion 23 and an actuatorhead 24 provided with two orifices 25. A front view of the top portion27 of said aerosol spray device 20 is shown in FIG. 2B. In thisembodiment the orifices 25 are placed on the top and bottom side of theactuator head 24 having the form of a plate along an axis beingsubstantially normal to the axis a-a of the actuator head 24. The fluidincluded in the spray bottle 21 is also in this embodiment dispersedsubstantially perpendicular to the axis of the actuator head 14, asshown in FIG. 2B.

[0047] The spray devices shown in FIGS. 1A-B and 2A-B are particularlyuseful for administration of a spray in front of the mandibular frontteeth behind the lips.

[0048] In FIG. 3A there is shown a third embodiment of an aerosol spraydevice 30 according to the invention. In analogy with the embodiment ofFIGS. 1A-B and 2A-B respectively, said spray device includes a spraybottle 31 and a top portion 37. The top portion 37 includes a capportion 32 and an actuator 36 according to the invention. The actuator36 includes a tube portion 33 and an actuator head 34 provided with sixorifices 35. A front view of the top portion 37 of said aerosol spraydevice 30 is shown in FIG. 3B. In this embodiment the orifices 35 areevenly spread round the periphery of actuator head 34. The fluidincluded in the spray bottle 31 is also in this embodiment dispersedsubstantially perpendicular to the axis of the actuator head 34.

[0049] The spray device according to FIGS. 3A-B is particularly usefulfor administration of a spray just behind the teeth.

[0050] In FIG. 4A there is shown a fourth embodiment of an aerosol spraydevice 40 according to the invention. In analogy with the embodiment ofFIGS. 1A-B, 2A-B and 3A-B, respectively, said spray device includes aspray bottle 41 and a top portion 47. The top portion 47 includes a capportion 42 and an actuator 46 according to the invention. The actuator46 includes a tube portion 43 and an actuator head 44 provided withthree orifices 45. A front view of the top portion 47 of said aerosolspray device 40 is shown in FIG. 4B. In this embodiment the orifices 45are placed in the lower part of the periphery of the actuator head 44.The fluid included in the spray bottle 41 in this embodiment isdispersed downwards in a half circle substantially perpendicular to theaxis of the actuator head 44.

[0051] The spray device according to FIGS. 4A-B is particularly usefulfor sublingual administration.

[0052] The actuator according to the invention may be constructed inmany different ways.

[0053] The spray actuator according to the invention comprises anactuator head having a defined axis and being provided with an orifice,where said orifice generates a spray or spray pattern directed in anangle of substantially 90±35 degrees from the actuator head axis.

[0054] The actuator may have different lengths and directions inrelation to the spray bottle. The actuator head may be constructed intodifferent forms, such as into the form of a divers mouthpiece or beingprovided with a flange in front of the actuator head with the aim ofcreating a distance between the lips and the teeth, thereby facilitatethe delivering of the spray. The actuator head may also be constructedin an arched or curved form to follow the teeth and the orifices maythen be distributed along part of or the whole arched or curved form.

[0055] The orifices may be of different size and shape, which willeffect the spray pattern dispensed from the orifices. The actuator headmay include one or more orifices. Preferable it includes many orifices,evenly distributed around the circumference of the actuator head. Thesizes and the shape of holes may vary and is defined according to whatis apropriate for the administration in question.

[0056] In one embodiment the actuator have a direction perpendicular tothe axis of the spray bottle, as shown in the appended drawings, and thespray is directed in an angle of substantially 90 degrees to the axisa-a of the actuator head. Another embodiment may be an embodiment, wherethe actuator is directed along the axis of the spray bottle and theactuator head is directed substantially perpendicular to the actuatorand axis of the spray bottle.

[0057] The spray bottle may be any known type, such as a pump spray orany other means for providing a spray. The spray may be provided bymeans of a pressurised gas.

[0058] The actuator may be made of any suitable material, such as aplastic material, or any other material well known within the art to besuitable for this type of device.

[0059] Mode of Administration

[0060] To obtain a local administration of the substance to the front ofthe oral cavity of a subject, the spray pattern delivering the substanceis preferably directed in about 90±35 degrees to the actuator tominimize and/or exclude deposition of the substance in the back of themouth. This will in turn reduce or substantially avoid the bad andunpleasant taste and irritating effect of a substance. A correctpositioning of the device according to the invention, such as a as shownin the appended drawing, will give an administration in front of theoral cavity of a subject. Specifically the aerosol spray is administeredto the front of the mandibular front teeth, i.e. in front of the teethbetween the lips and the teeth, just behind the teeth or under thetongue.

[0061] Thus, in one embodiment the spray pattern delivering thesubstance is directed at an angle between about 55 and 125 degrees tothe axis a-a of the end of the actuator nearest to the mouth.

[0062] In a further embodiment the spray pattern delivering thesubstance is directed at an angle between about 90 and about 125 degreesto the axis a-a of the end of the actuator nearest to the mouth; i.e.the spray is delivered upwards and obliquely backwards.

[0063] In a still further embodiment the spray pattern delivering thesubstance is directed at an angle of about 90 degrees to the axis a-a ofthe actuator; i.e. the spray is delivered substantially neitherbackwards nor forwards.

[0064] The examples below show that administration of an aerosolnicotine spray to the front of the oral cavity by means of an aerosolspray device adapted for such an administration reduces or substantiallyavoids the bad and unpleasant taste and irritating effect of asubstance, while simultaneously giving substantially the same absorptionand thereby effect of said substance.

[0065] Substances to be Administered

[0066] Suitable substances for distribution with the actuator accordingto the invention are any drug or medicament suitable for oraladministration giving a bad and unpleasant taste and/or irritatingeffect. Examples of such substances are alkaloids, such as nicotine,nicotine salts and esters, other nicotine derivatives, lobeline,lobeline salts and esters, other lobeline derivatives; meclozinediphenhydralamine and promethazin.

[0067] Nicotine is a good example of an irritating substance with a lesspleasant taste. Administering such substances via a mouth spray, vapouror aerosol is problematic. When ingested in larger doses, nicotine is ahighly toxic poison that causes vomiting and nausea, headaches, stomachpains, and, in severe cases, convulsions, paralysis, and death. Eveningested in minor doses, nicotine is still an irritating, strong and badtasting compound causing e.g. irritation in the oral cavity andrespiratory tracts. In order to reduce or avoid such irritation thesubstance in e.g. a spray should be administered to the frontal part ofthe mouth. The more frontal the less irritation and bad taste.

[0068] When administering nicotine it may be in the form of the freebase.

[0069] The active substance, such as nicotine or any of the substancesmentioned below, may be administered together with any suitable additiveknown within the art, such as flavourings, preservatives and alcohol.

[0070] Administration Methods

[0071] The invention refers to a method for oral administration of asubstance to a subject, comprising delivering an aerosol spraycontaining the substance to the front of the oral cavity of the subject.

[0072] The substance may be any substance as described under Substancesto be administered above.

[0073] In one embodiment the invention refers to a method for oraladministration of nicotine to a subject, comprising delivering anaerosol spray containing nicotine to the front of the oral cavity of thesubject.

[0074] In a further embodiment the invention refers to a method ofassisting in the reduction of the desire of a subject to use nicotine ornicotine containing compositions, comprising delivering a nicotinecontaining aerosol spray to the front of the oral cavity of the subject.

[0075] The nicotine containing aerosol spray may be administered to thefront of the mandibular front teeth, i.e. in front of the teeth betweenthe lips and the teeth, to the area just behind the teeth or under thetongue. The doses of nicotine to be administered are well known withinthe art. Typical examples are 0.5-6 mg doses of nicotine, specifically2-4 mg doses of nicotine.

[0076] The use of nicotine or a nicotine containing composition may bethe use of cigarettes, cigars, snuff, chewing tobacco and the like.

EXAMPLES Example 1

[0077] The effect of administering 2 mg of nicotine at different sitesin the mouth was studied in a study involving eight volunteer smokers.Each of 1A, 1B and 1C include all eight smokers. There was a three hoursinterval between the three administration conditions. The nicotine wasadministered in the form of a spray including in volume %: Nicotine 1.45% Alcohol 79.71% Glycerine 14.78% Flavour  3.94% Saccharine  0.12%

[0078] In 1A and 1B the nicotine was administered to the followingsites: 1A. in front of the mandibular front teeth, 1B below the tongue.In 1C, the control group, the nicotine spray was administered in theordinary way according to general instructions given for nicotine spraysaiming at the sides of the mouth. The degree of irritation andunpleasant taste, respectively was rated at 5 min after applicationusing a VAS (visual analogue scale, 100 mm; 0 mm means no irritation orunpleasant taste and 100 mm means maximal irritation and unpleasanttaste, respectively). Blood tests were carried out immediately beforeand 15 minutes after the administration of the nicotine dose and thenicotine plasma levels were determined as the Δ plasma nicotine value.

[0079] The device used was a standard Nussbaum & Guhl pump.

[0080] Results: Irritation Unpleasant Δ plasma Administration (mm) SD*taste (mm) SD* nicotine ng/ml 1A 63 14.6 61 10.4 5.5 1B 59 12.9 63 9.85.4 1C 82 13.1 71 12.6 4.3

[0081] As to the degree of irritation 1C was significantly higher thanboth 1A and 1B (p<0.01, two tailed test). As to the degree of unpleasanttaste 1C was significantly higher than 1A (p<0.01, two tailed test) and1C was also higher than 1B (p<0.05, two tailed test).

[0082] Example 1 shows that an administration of a nicotine spray in thefront of the oral cavity gives less irritation and unpleasant tastecompared to ordinary administration in the whole oral cavity. Theabsorption of nicotine, i.e. the effect of the nicotine is however notreduced.

Example 2

[0083] A second experiment was performed using ten volunteer smokers.Each of 2A, 2B and 2C included all ten smokers. As in example 1 therewas a three hours interval between the administration conditions. In 2Aa 2 mg nicotine mouth spray using a standard Nussbaum & Guhl pump wasused and the dose was administered in the same ordinary way according togeneral instructions given for nicotine sprays as in 1C above. In 2B 2mg and in 2C 4 mg of nicotine was given by means of the device shown inFIG. 1A. The doses 2A and 2B were administered in front of themandibular front teeth.

[0084] Said nicotine spray had the same composition as the spray inexample 1 and irritation, unpleasant taste as well as Δ plasma nicotinewere rated and measured in the same way as in example 1.

[0085] Results: Irritation Unpleasant Δ plasma Administration (mm) SD*taste (mm) SD* nicotine ng/ml 2A 64 10.8 62 11.3 5.7 2B 41 9.0 43 8.95.5 2C 65 11.0 61 13.0 7.2

[0086] As to the degree of both irritation and unpleasant taste 2A wassignificantly higher than 2B (p<0.01, two tailed test) and the values of2C was also significantly higher than 2B (p<0.01, two tailed test). Whencomparing 2A and 2B this example 2 also shows that administration of thenicotine to the front of the oral cavity (2B), here the front of themandibular front teeth, gives much less irritation and unpleasant tastecompared to ordinary administration in the whole oral cavity (2A), stillhaving substantially the same effect. 2C shows that a dose of 4 mg(double dose) administered in the front of the mandibular front teethdoes not give more irritation and unpleasant taste than half the dose (2mg) administered in the ordinary way into the whole oral cavity.

Example 3

[0087] The experiment described in Example 2 was repeated using tenvolunteer smokers. In 3A a 2 mg nicotine mouth spray using a standardNussbaum & Guhl pump was used and in 3B 2 mg and 3C 4 mg of nicotine wasgiven by means of the aerosol spray device shown in FIG. 1A. Allnicotine doses (3A-3C) were administered below the tongue.

[0088] Results: Irritation Unpleasant Δ plasma Administration (mm) SD*taste (mm) SD* nicotine ng/ml 3A 69 13.3 62 12.8 6.9 3B 46 9.8 44 10.47.7 3C 71 14.5 63 13.8 10.1

[0089] As to the degree of both irritation and unpleasant taste 3A wassignificantly higher than 3B (p<0.01, two tailed test) and the values of3C was also significantly higher than 3B (p<0.01, two tailed test).

[0090] Example 3 shows that administration of the nicotine spray bymeans of a device, such as a device according to the invention, adaptedfor administration of the spray into the very front of the oral cavityreduces both irritation and unpleasant taste, but not the absorption ofnicotine.

1. An aerosol spray device for administering a substance to the oralcavity of a subject, said aerosol spray device (10, 20, 30, 40)comprising an actuator (16, 26, 36, 46) having an actuator head (14, 24,34, 44) with a defined axis (a-a) and at least one orifice (15, 25, 35,45), the actuator head being constructed to dispense the aerosol spraycontaining the substance in the front of the oral cavity of the subject.2. The device according to claim 1, wherein the front of the oral cavityis in front of the mandibular front teeth, the area just behind theteeth or under the tongue.
 3. The device according to any of claims 1-2,wherein the actuator head (14, 24, 34, 44) dispenses the aerosol sprayin a direction, which forms an angle of substantially 90±35 degrees withthe actuator head axis (a-a).
 4. The device according to any of claims1-3, wherein the substance is a substance having a disagreeable tasteand/or being a source of irritation.
 5. The device according to any ofclaims 1-4, wherein the substance comprises a substance selected fromthe group consisting of alkaloids, such as nicotine, nicotinederivatives, nicotine salts, lobeline, lobeline derivatives or lobelinesalts; meclozine diphenhydralamine and promethazin.
 6. The deviceaccording to claim 5, wherein the substance is nicotine.
 7. The deviceaccording to claim 6, wherein nicotine is in the form of the free base.8. The device according to any of claims 1-7, wherein the actuator head(14, 24, 34, 44) is provided with two or more orifices (15, 25, 35, 45).9. The device according to any of claims 1-8, wherein the orifices (15,25, 35) are evenly spread around the periphery of the actuator head (14,24, 34)
 10. The device according to any of claims 1-8, wherein theorifices (15, 25, 35) are placed in the lower part of the actuator head(14, 24, 34).
 11. An actuator (16, 26, 36, 46) having an actuator head(14, 24, 34, 44) and an orifice (15, 25, 35, 45), and being adapted tobe used in an aerosol spray device as defined in any of claims 1-9. 12.A top portion (17, 27, 37, 47) including an actuator as claimed in claim11.
 13. A method for oral administration of a substance to a subject,comprising delivering an aerosol spray containing the substance to thefront of the oral cavity of the subject.
 14. The method according toclaim 13, wherein the front of the oral cavity is the area in front ofthe mandibular front teeth, the area just behind the teeth or under thetongue.
 15. The method according to any of claims 13-14, wherein thesubstance is a substance having a disagreeable taste and/or being asource of irritation.
 16. The method according to claim 15, wherein thesubstance is selected from the group consisting of alkaloids, such asnicotine, nicotine derivatives, nicotine salts, lobeline, lobelinederivatives or lobeline salts; meclozine diphenhydralamine andpromethazin.
 17. The method according to claim 16, wherein the substanceis nicotine.
 18. The method according to claim 17, wherein the substanceis nicotine in the form of the free base.
 19. A method of assisting inthe reduction of the desire of a subject to use nicotine or nicotinecontaining compositions, comprising delivering a nicotine containingaerosol spray to the front of the oral cavity of the subject.
 20. Themethod of claim 19, wherein the front of the oral cavity is the area infront of the mandibular front teeth, the area just behind the teeth orunder the tongue.
 21. The method any of claims 19-20, wherein thenicotine containing aerosol spray contains nicotine in the form of thefree base.